Summary
A 59‐year‐old patient with diabetes mellitus had been treated with human recombinant insulin for 4 years. He developed a solid mass on his left abdomen at the insulin injection site, which ...had an overlying pigmented verrucous plaque and keratinized papules, similar to acanthosis nigricans (AN). On histological examination, the mass was found to contain a deposit of amyloid in the dermis, with hyperkeratosis, papillomatosis and acanthosis in the epidermis. Using immunohistochemistry, the amyloid deposits were found to be positive for insulin. A few cases of localized insulin‐derived amyloid deposits at injection sites have been reported previously, but none had significant epidermal changes. The coexistence of dermal insulin‐derived amyloidosis and an overlying AN‐like change, as found in our patient, has not been reported previously, to our knowledge. The presence of a tumour‐like lesion at the injection site should be carefully examined, as injection of insulin into amyloid deposits can result in insulin resistance.
Background and purpose
Corticobasal syndrome (CBS) is pathologically characterized by tau deposits in neuronal and glial cells and by reactive astrogliosis. In several neurodegenerative disorders, ...18F‐THK5351 has been observed to bind to reactive astrocytes expressing monoamine oxidase B. In this study, the aim was to investigate the progression of disease‐related pathology in the brains of patients with CBS using positron emission tomography with 18F‐THK5351.
Methods
Baseline and 1‐year follow‐up imaging were acquired using magnetic resonance imaging and positron emission tomography with 18F‐THK5351 in 10 subjects: five patients with CBS and five age‐matched normal controls (NCs).
Results
The 1‐year follow‐up scan images revealed that 18F‐THK5351 retention had significantly increased in the superior parietal gyrus of the patients with CBS compared with the NCs. The median increases in 18F‐THK5351 accumulation in the patients with CBS were 6.53% in the superior parietal gyrus, 4.34% in the precentral gyrus and 4.33% in the postcentral gyrus. In contrast, there was no significant increase in the regional 18F‐THK5351 retention in the NCs.
Conclusions
Longitudinal increases in 18F‐THK5351 binding can be detected over a short interval in the cortical sites of patients with CBS. A monoamine oxidase B binding radiotracer could be useful in monitoring the progression of astrogliosis in CBS.
The formation of neurofibrillary tangles is believed to contribute to the neurodegeneration observed in Alzheimer's disease (AD). Postmortem studies have shown strong associations between the ...neurofibrillary pathology and both neuronal loss and the severity of cognitive impairment. However, the temporal changes in the neurofibrillary pathology and its association with the progression of the disease are not well understood. Tau positron emission tomography (PET) imaging is expected to be useful for the longitudinal assessment of neurofibrillary pathology in the living brain. Here, we performed a longitudinal PET study using the tau-selective PET tracer 18FTHK-5117 in patients with AD and in healthy control subjects. Annual changes in 18FTHK-5117 binding were significantly elevated in the middle and inferior temporal gyri and in the fusiform gyrus of patients with AD. Compared to patients with mild AD, patients with moderate AD showed greater changes in the tau load that were more widely distributed across the cortical regions. Furthermore, a significant correlation was observed between the annual changes in cognitive decline and regional 18FTHK-5117 binding. These results suggest that the cognitive decline observed in patients with AD is attributable to the progression of neurofibrillary pathology. Longitudinal assessment of tau pathology will contribute to the assessment of disease progression and treatment efficacy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background and purpose
Corticobasal syndrome (
CBS
) is pathologically characterized by tau deposits in neuronal and glial cells and by reactive astrogliosis. In several neurodegenerative disorders,
...18
F‐
THK
5351 has been observed to bind to reactive astrocytes expressing monoamine oxidase B. In this study, the aim was to investigate the progression of disease‐related pathology in the brains of patients with
CBS
using positron emission tomography with
18
F‐
THK
5351.
Methods
Baseline and 1‐year follow‐up imaging were acquired using magnetic resonance imaging and positron emission tomography with
18
F‐
THK
5351 in 10 subjects: five patients with
CBS
and five age‐matched normal controls (
NC
s).
Results
The 1‐year follow‐up scan images revealed that
18
F‐
THK
5351 retention had significantly increased in the superior parietal gyrus of the patients with
CBS
compared with the
NC
s. The median increases in
18
F‐
THK
5351 accumulation in the patients with
CBS
were 6.53% in the superior parietal gyrus, 4.34% in the precentral gyrus and 4.33% in the postcentral gyrus. In contrast, there was no significant increase in the regional
18
F‐
THK
5351 retention in the
NC
s.
Conclusions
Longitudinal increases in
18
F‐
THK
5351 binding can be detected over a short interval in the cortical sites of patients with
CBS
. A monoamine oxidase B binding radiotracer could be useful in monitoring the progression of astrogliosis in
CBS
.
Corticobasal syndrome (CBS) is pathologically characterized by tau deposits in neuronal and glial cells and by reactive astrogliosis. In several neurodegenerative disorders,
F-THK5351 has been ...observed to bind to reactive astrocytes expressing monoamine oxidase B. In this study, the aim was to investigate the progression of disease-related pathology in the brains of patients with CBS using positron emission tomography with
F-THK5351.
Baseline and 1-year follow-up imaging were acquired using magnetic resonance imaging and positron emission tomography with
F-THK5351 in 10 subjects: five patients with CBS and five age-matched normal controls (NCs).
The 1-year follow-up scan images revealed that
F-THK5351 retention had significantly increased in the superior parietal gyrus of the patients with CBS compared with the NCs. The median increases in
F-THK5351 accumulation in the patients with CBS were 6.53% in the superior parietal gyrus, 4.34% in the precentral gyrus and 4.33% in the postcentral gyrus. In contrast, there was no significant increase in the regional
F-THK5351 retention in the NCs.
Longitudinal increases in
F-THK5351 binding can be detected over a short interval in the cortical sites of patients with CBS. A monoamine oxidase B binding radiotracer could be useful in monitoring the progression of astrogliosis in CBS.
In vivo detection of amyloid deposits is useful for early diagnosis of Alzheimer’s disease (AD) and for prediction of potential converters from mild cognitive impairment (MCI) to AD. Our original ...imaging probe, 11CBF-227, has been shown to be useful for clinical evaluation of AD, MCI and various neurodegenerative disorders using positron emission tomography (PET). Purpose of the present study is to examine methods for quantitative analysis of amyloid deposition in human brain using PET and 11CBF-227 as well as our newer compound 18FFACT.
For 11CBF-227, six AD patients (mean age: 73.0 y.o.) and six healthy controls (mean age: 61.3 y.o.) were studied. For 18FFACT, ten AD patients (mean age: 74.5 y.o.) and six healthy controls (mean age: 68.3 y.o.) were studied in the present study. Regions of interest (ROIs) were placed on various cortical and subcortical regions in dynamic PET images of 60- min- and 90-min-long duration, based on the coregistered MRI T1 images. Results of quantification using arterial inputs were compared to those calculated by Logan graphical analysis with arterial data (LGA) and with the reference data (LGAR), and to those calculated by full kinetic analysis based on 1- and 2- tissue compartmental models (1TM and 2TM). These results were compared to the ratio of standardized uptake values (SUV) in the cortex to that in the cerebellum, as well.
11CBF-227 displayed significantly higher distribution volume ratio (DVR) values in AD patients than in controls in various cortical regions such as the cingulate, temporal and occipital regions, especially in the temporo-occipital regions. The preliminary results of quantitative analysis of 18FFACT showed nearly the same findings as those of 11CBF-227. Considering the longer half-life of 18F nuclide (110 min) than that of 11C nuclide (20 min), this tracer could be used as a diagnosing pharmaceutical for delivery.
A 60-year-old man presented with postoperative recurrence of intrahepatic cholangiocarcinoma with right portal vein tumor thrombosis (PVTT). After failure of standard chemotherapy, a liver biopsy ...showed that his microsatellite instability (MSI) status was high. Treatment with the immune checkpoint inhibitor (ICI) pembrolizumab was commenced, which resulted in a partial response and resolution of the PVTT. There were no significant immune-related adverse events. According to recently published reports, the frequency of MSI-high biliary tract cancer (BTC) is about 0-2.1%, which is extremely rare. However, ICIs may be effective in patients with MSI-high BTC, such as the present patient.
18FTHK5351, a recently-developed positron emission tomography (PET) tracer for measuring tau neurofibrillary tangle accumulation, may help researchers examine aging, disease, and tau pathology in ...living human brains. We examined THK5351 tracer pharmacokinetics to define an optimal acquisition time for static late images.
Primary measurements were calculation of regional values of distribution volume ratios (DVR) and standardized uptake value ratios (SUVR) in 6 healthy older control and 10 Alzheimer's disease (AD) participants. We examined associations between DVR and SUVR, searching for a 20 min SUVR time window that was stable and comparable to DVR. We additionally examined diagnostic group differences in this 20 min SUVR.
In healthy controls, 18FTHK5351 uptake was low, with increased temporal relative to frontal binding. In AD, regional uptake was substantially higher than in healthy controls, with temporal exceeding frontal binding. Retention in cerebellar gray matter, which was used as the reference region, was low compared to other regions. Both DVR and SUVR values showed minimal change over time after 40 min. SUVR 20-40, 30-50, and 40-60 min were most consistently correlated with DVR; SUVR 40-60 min, the most stable time window, was used in further analyses. Significant (AD > healthy control) group differences existed in temporoparietal regions, with marginal medial temporal differences. We found high basal ganglia SUVR 40-60 min signal, with no group differences.
We examined THK5351, a new PET tracer for measuring tau accumulation, and compared multiple analysis methods for quantifying regional tracer uptake. SUVR 40-60 min performed optimally when examining 20 min SUVR windows, and appears to be a practical method for quantifying relative regional tracer retention. The results of this study offer clinical potential, given the usefulness of THK5351-PET as a biomarker of tau pathology in aging and disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Recent positron emission tomography (PET) studies have demonstrated the accumulation of tau PET tracer in the affected region of progressive supranuclear palsy (PSP) cases. To confirm the binding ...target of radiotracer in PSP, we performed an imaging-pathology correlation study in two autopsy-confirmed PSP patients who underwent
FTHK5351 PET before death. One patient with PSP Richardson syndrome showed elevated tracer retention in the globus pallidus and midbrain. In a patient with PSP-progressive nonfluent aphasia,
FTHK5351 retention also was observed in the cortical areas, particularly the temporal cortex. Neuropathological examination confirmed PSP in both patients. Regional
FTHK5351 standardized uptake value ratio (SUVR) in antemortem PET was significantly correlated with monoamine oxidase-B (MAO-B) level, reactive astrocytes density, and tau pathology at postmortem examination. In in vitro autoradiography, specific THK5351 binding was detected in the area of antemortem
FTHK5351 retention, and binding was blocked completely by a reversible selective MAO-B inhibitor, lazabemide, in brain samples from these patients. In conclusion,
FTHK5351 PET signals reflect MAO-B expressing reactive astrocytes, which may be associated with tau accumulation in PSP.
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